The proposed research has as its objectives to elucidate the underlying biochemical, ultrastructural, and regulatory mechanisms involved in the formation of glycosphingolipids (gangliosides) of the mammalian cell surface. The ganglioside changes which accompany the oncogenic transformation will serve as a model for the study of the regulation and formation of one class of gene products, the complex heterosaccharide chains of the glycoproteins and glycolipids, whose formation is altered as one result (direct or indirect) of transformation. To investigate early changes in glycosphingolipids and glycosphingolipid biosynthetic enzymes in precancerous hyperplastic liver tissue and nodules as well as in both non-invasive and invasive hepatomas, the carcinogen N-2-fluorenylacetamide was administered orally to rats. Neoplastic tissues are being compared with control, fetal, neonatal, and precancerous liver tissues. Development of the tumors is slow such that temporal changes in the biochemical and morphologic development during tumorigenesis can be identified. By following step-by-step the events leading to depletion of specific glycolipid glycosyltransferases and attendant cell surface changes, we anticipate that we will eventually obtain sufficient information to elucidate which of the many changes may qualify as minimum deviation events.